The neuropeptide luteinizing hormone-releasing hormone (LHRH) is the prime regulator of gonadal function in vertebrates. A major effort of our laboratory is directed to understand the mechanisms regulating the secretion and actions of LHRH. Concerning the basic aspects of the LHRH neuronal system, some very exciting advances were recently made in our laboratory. In regards to the functional architecture of this system, an important discovery was made with the descriptions of the co-localization of galanin, a gut-brain peptide, in a subset of preoptic LHRH neurons. Important sex differences were observed in the number of neurons co-expressing LHRH and galanin, with female brains containing 2-3 fold higher number of these neurons. In view of the well known stimulatory effects of estrogens on galanin gene expression, these studies offer a new insight into the possible mechanisms mediating estrogen effects on neuroendocrine neuronal systems regulating reproductive functions. Another major advance in the study of LHRH physiology is represented by the establishment in the laboratory of a neuronal cell line (GTI) which produces and secretes LHRH. Under appropriate culture conditions, these cells have been shown to secrete LHRH in a pulsatile fashion, a feature that provides the first demonstration that LHRH cells represent the pulse generator that drives the pulsatile secretion of gonadotropins. Experiments under way are directed to the more fundamental questions concerning the molecular and cellular aspects of the activity of these neurons. The results of these studies should have profound implications for the understanding of the neurobiology of neuronal systems with intrinsic rhythmic activity. A clinical research program now under way in our lab is directed to gain more information about the neuroendocrine mechanisms controlling the normal, or abnormal, onset of puberty in humans and to obtain new information on the effects of LHRH analogs on different endocrine parameters.